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Biomedical subjects

A Saxena

Publications and source records attributed to A Saxena.

At least 55 records · Page 3Linked to original sources

Posttransplant diffuse large B-cell lymphoma of "lymphomatoid granulomatosis" type.

The exact relationship between lymphomatoid granulomatosis (LyG) and posttransplant lymphoproliferative disorders (PTLDs) is not clear. Both are observed in immunodeficient patients and are Epstein-Barr virus driven. These disorders are, however, considered distinct based upon the immune response elicited; LyG is T-cell rich while PTLDs are T-cell poor. We describe a case of LyG-type diffuse large B-cell lymphoma (DLBCL) in a lung transplant recipient. The unusual features include rare occurrence of LyG in a posttransplant setting, systemic involvement by LyG variant of DLBCL in a solid organ transplant recipient, paucity of T-cells in this LyG type lymphoma, and subcutaneous panniculitic pattern in a B-cell lymphoproliferative disorder. This first report of systemic LyG variant of DLBCL in a posttransplant setting has features suggesting similarities and overlap between LyG and PTLD.

DNA, Neoplasm↗

Omphalocele: clinical review and surgical experience using dura patch grafts.

Over a period of 15 years we surgically treated 50 cases of omphaloceles. The pathology occurred more frequently in boys (n = 30) than in girls (n = 20). The mean birth weight was 2995 g and mean gestational age was 38 weeks. Four infants (8%) were delivered vaginally and the rest (92%) by cesarian section. Eleven infants (22%) underwent primary closure, but in 20 infants (40%) with larger defects a primary closure of the skin was possible; however, a single solvent-dried dura graft implant was employed for the fascia enlargement. The remaining 19 infants (38%) had extremely large defects, and optimal closure of the defect required a two layered graft implantation. Twenty-five infants (50%) had associated anomalies, the majority being congenital cardiac anomalies. Five patients (10%) required secondary laparotomies due to bowel associated complications. Four patients (8%) experienced non-bowel-associated complications. The average postoperative mechanical ventilation required was for a period of 3.2 days and the average hospital stay was 45.7 days. The overall mortality rate was 8% (n = 4) and was largely due to severe congenital heart anomalies. Solvent-dried dura was successfully employed in the management of the larger defects with no major complications; only one patient (2%) had a local abscess around the area of the implant and was managed conservatively. Our experience favors the employment of solvent-dried dura graft implants for the repair of large omphaloceles. The solvent-dried dura grafts are biomaterials that promote rapid scar formation and integration with the adjacent skin tissue and do not produce any foreign body reactions at the site of implantation.

Birth Weight↗

Usefulness of an inexpensive, Paracheck test in detecting asymptomatic infectious reservoir of plasmodium falciparum during dry season in an inaccessible terrain in central India.

OBJECTIVES: The performance of a new indigenous rapid diagnostic test, Paracheck Pf was evaluated in detection of Plasmodium falciparum in asymptomatic children in remote forest villages of Mandla district, central India to determine the lower limits of sensitivity and specificity of rapid test. METHODS: A finger prick blood sample was collected to prepare blood smear and for testing with the Paracheck test. The blood smears were read by an experienced technician blinded to the Paracheck results. The figures for specificity, sensitivity, accuracy and predictive values were calculated using microscopy as gold standard. RESULTS: The new diagnostic test had a sensitivity of 94% and a specificity of 89%. The positive and negative predictive values were 71% and 98%, respectively. The J -index was 0.83%. CONCLUSION: The rapid test was found to be very easy to perform and the result could be read reliably by field workers. The field evaluation with this new inexpensive test, ($0.65/test) indicates that it could be used as an epidemiological tool in the management of malaria particularly in areas where microscopy is not operationally feasible to attain the goal of the roll back malaria initiative.

Adolescent↗

Modulation of ovarian function in female dogs immunized with bovine luteinizing hormone receptor.

Adult female dogs were immunized with 0.5 mg bovine luteinizing hormone receptor (LH-R) encapsulated in a silastic subdermal implant and subsequently with four intramuscular booster injections of 0.1 mg LH-R each. Circulating LH-R antibody was detected in the sera 3 weeks post-implant. The appearance of LH-R antibody was associated with a decline in the serum progesterone concentrations to a range of 0-0.5 ng/ml until day 365 in the immunized dogs in comparison with a range of 5-10 ng in the control animals, suggesting a lack of ovulation and corpus luteum function in immunized dogs. The immunized dogs did not show signs of 'standing heat' and failed to ovulate when induced by LH-RH challenge. Serum oestradiol levels, however, remained in the range of 30-40 pg/ml in both the immunized and the control dogs. With the decline in the antibody titres, the hormonal profile and vaginal cytology returned to a fertile state and the dogs exhibited signs of 'standing heat', as well as vaginal bleeding. Dogs immunized with LH-R did not show any serious metabolic, local or systemic adverse effects. The hypothalamic--pituitary gonadal axis remained intact as indicated by little difference in pituitary LH levels between control and immunized animals, and by the release of LH by LH-RH challenge. These studies demonstrate that active immunization of female dogs with LH-R could immunomodulate ovarian function to cause a reversible state of infertility. It may be postulated that, due to extensive interspecies homology, a recombinant LH receptor-based immunocontraceptive vaccine may also be effective in other vertebrates.

Adjuvants, Immunologic↗

Achilles tendinopathy: some aspects of basic science and clinical management.

Achilles tendinopathy is prevalent and potentially incapacitating in athletes involved in running sports. It is a degenerative, not an inflammatory, condition. Most patients respond to conservative measures if the condition is recognised early. Surgery usually involves removal of adhesions and degenerated areas and decompression of the tendon by tenotomy or measures that influence the local circulation.

Achilles Tendon↗

Study of trace element correlations with drought tolerance in different sorghum genotypes using energy-dispersive X-ray fluorescence technique.

Drought-tolerant and drought-susceptible genotypes of sorghum (Sorghum bicolor L. Monech) were analyzed by the energy-dispersive X-ray fluorescence (EDXRF) technique to study the correlation of trace elements with drought-tolerance capacities. Samples prepared from mature seeds, young seedlings, and old plants were analyzed using a 109Cd radioisotope source and a Si(Li) semiconductor detector of resolution 170 eV for 5.9-keV MnKalpha X-rays. Elements such as K, Fe, Cu, Zn, Rb and Sr and Y were found to be present in varying concentrations in different samples. The trace element profile studied in the seeds of 11 genotypes and in seedlings (young and old) of 4 sorghum genotypes showed considerable variation. The genotype Arfa Gadamak (AG) showed a distinct presence of a high level of Zn in its young seedling. It was observed that in most of the genotypes (seeds), K and Fe concentrations were more in the tolerant genotype as compared to the susceptible type. The concentration of Fe decreased with maturity in the tolerant group and it increased with maturity in the susceptible group.

Adaptation, Biological↗

Effects of competing short- and long-range dispersive interactions on discrete breathers.

The discrete nonlinear Schrödinger equation with competing short-range and long-range interactions is considered in spatial dimensions d> or =2. This model equation is derived for a situation of two linearly coupled excitations (independently of dimension), and we analytically and numerically study its properties in 2+1 dimensions. We analyze theoretically and demonstrate numerically the dependence of the discrete breather solutions on the amplitude and range of the interactions. We find that complete suppression of the existence thresholds obtained recently for short-range interactions can be achieved beyond a critical value of the amplitude or of the range of the long-range kernel. For supercritical values of the corresponding parameters, staggered branches of solutions are obtained both in theory as well as in the numerical experiment.

Journal Article↗

Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells.

Dendritic cells (DCs) that acquired antigen from apoptotic tumor cells are able to induce major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes and antitumor immunity. In the present study, we investigated the efficiency of antitumor immunity derived from DCs that had phagocytosed apoptotic/necrotic BL6-10 melanoma cells compared with that of DCs pulsed with the tumor mTRP2 peptide. Our data showed that phagocytosis of apoptotic/necrotic tumor cells resulted in maturation of DCs with up-regulated expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor], chemokines (MIP-1alpha, MIP-1beta and MIP-2), the CC chemokine receptor CCR7 and the cell surface molecules (MHC class II, CD11b, CD40 and CD86), and down-regulated expression of the CC chemokine receptors CCR2 and CCR5. These mature DCs displayed enhanced migration toward the CC chemokine MIP-3beta in a chemotaxis assay in vitro and to the regional lymph nodes in an animal model in vivo. Our data also showed that vaccination with DCs that had phagocytosed apoptotic/necrotic BL6-10 cells was able to (i) more strongly stimulate allogeneic T-cell proliferation in vitro, (ii) induce an in vivo Th1-type immune response leading to more efficient tumor-specific cytotoxic CD8(+) T-cell-mediated immunity and (iii) eradicate lung metastases in all 6 vaccinated mice compared with mice vaccinated with DCs pulsed with the tumor mTRP2 peptide, in which lung metastases were reduced (mean number of 16 per mouse) but not completely eradicated. Therefore, DCs that had phagocytosed apoptotic/necrotic tumor cells appear to offer new strategies in DC cancer vaccines.

Animals↗

Interaction between sine-Gordon breathers.

Using the exact breather lattice solution of the sine-Gordon equation, we obtain the asymptotic interaction between two breathers. We identify the exponential dependence of the interaction on the breather separation as well as its power-law dependence on the breather frequency. Numerical simulation of the breather lattice demonstrates its instability. However, stabilization of such structures is found to be feasible through ac driving and damping. Finally, other limits of the original periodic solution are traced, obtaining the leading-order terms in the interaction between "pseudosphere" solutions and kink-antikink pairs.

Journal Article↗

Three-dimensional elastic compatibility and varieties of twins in martensites.

We model a cubic-to-tetragonal martensitic transition by a Ginzburg-Landau free energy in the symmetric strain tensor. We show in three dimensions (3D) that solving the St. Venant compatibility relations for strain, treated as independent field equations, generates three anisotropic long-range potentials between the two order parameter components. These potentials encode 3D discrete symmetries, express the energetics of lattice integrity, and determine 3D textures. Simulation predictions include twins with temperature-varying orientation, helical twins, competing metastable states, and compatibility-induced elastic frustration. Our approach also applies to improper ferroelastics.

Journal Article↗

Novel and potent tacrine-related hetero- and homobivalent ligands for acetylcholinesterase and butyrylcholinesterase.

Based upon synthetic and biochemical results, a novel and potent tacrine analogue and heterobivalent analogues of tacrine, were designed. The role played by the amino groups of homo- and heterobivalent ligands in the interaction with the peripheral and catalytic sites of AChE and BuChE were investigated. The syntheses of these materials together with the results of AChE/BuChE inhibition assays are detailed.

Acetylcholinesterase↗

Detection of coronary artery anomalies in tetralogy of Fallot using a specific angiographic protocol.

Patients with tetralogy of Fallot were studied with a prespecified angiographic protocol aimed to delineate the types and incidence of coronary artery anomalies and to look for any correlation with other abnormalities detected by simultaneous detailed angiography. The incidence of coronary anomalies was found to be 7.0%; no association was found with these anomalies with any of the other abnormalities detected.

Abnormalities, Multiple↗

The Leishmania genome project: new insights into gene organization and function.

The sequencing of Leishmania major Friedlin chromosome 1 (Chr1), Chr3, and Chr4 has been completed. and several other chromosomes are well underway. The complete genome sequence should be available by 2003. Over 1,000 full-length new genes have been identified, with the majority (approximately 75%) having unknown function. Many of these may be Leishmania (or kinetoplastid) specific. Most interestingly, the genes are organized into large (> 100-500 kb) polycistronic clusters of adjacent genes on the same DNA strand. Chr1 contains two such clusters organized in a "divergent" manner, i.e., the mRNAs for the two sets of genes are both transcribed towards the telomeres. Nuclear run-on analysis suggests that transcription is initiated in both directions within the "divergent" region. Chr3 and Chr4 contain two "convergent" clusters, with a single "divergent" gene at one telomere of Chr3. Sequence analysis of several genes from the LD1 region of Chr35 indicates a high degree of sequence conservation between L. major and L. donovani/L. infantum within protein-coding open reading frames (ORFs), with a lower degree of conservation within the non-coding regions. Immunization of mice with recombinant antigen from two of these genes, BTI (formerly ORFG) and ORFF, results in significant reduction in parasite burden following Leishmania challenge. Recombinant ORFF antigen shows promise as a serodiagnostic. We have also developed a tetracycline-regulated promoter system, which allows us to modulate gene expression in Leishmania.

Animals↗

One and a half ventricle repair with pulsatile bidirectional Glenn: results and guidelines for patient selection.

BACKGROUND: The guidelines for performing a one and a half ventricle repair with pulsatile bidirectional Glenn remains controversial. This retrospective report summarizes the experience of a single institution, with an attempt at providing an answer. METHODS: Fifty consecutive patients, aged 4 months to 42 years, underwent intracardiac repair along with a superior cavopulmonary connection. Twenty-seven of the patients had had previous surgical palliation. Repair consisted of patch closure of the ventricular septal defect (n = 25), tricuspid valve repair (n = 26), reconstruction of the right ventricular outflow tract (n = 34), transpulmonary annular patch (n = 34), right ventricle to pulmonary artery homograft conduit (n = 4), and concomitant repair of atrioventricular canal (n = 9). Ten patients were left with a fenestration in the atrial septum. RESULTS: There were six hospital deaths (12%) and two late deaths (4.5%). Forty-two survivors were followed from 8 months to 116 months. Eighty-eight percent are in functional class I. Actuarial survival at 97 months was 74%. CONCLUSIONS: Moderate right heart hypoplasia constitutes a safe anatomic category for a pulsatile bidirectional Glenn. It is advisable not to proceed with a one and a half ventricle repair if postoperative residual pulmonary artery hypertension is anticipated. Patients requiring an intricate intracardiac repair and those with concomitant right heart hypoplasia may be better suited for a Fontan type of repair to reduce the complexity of the procedure.

Actuarial Analysis↗

Factors influencing late course of residual valvular and infundibular gradients following pulmonary valve balloon dilatation.

BACKGROUND: Though acute and follow-up benefits of pulmonary valve balloon dilatation (PVBD) for pulmonic valve stenosis are well known, the late course of residual gradients at individual valvular and infundibular levels is not well described. Furthermore, the factors influencing this late course have not been studied. MATERIALS AND METHODS: We assessed the transpulmonary gradients by echo-Doppler in 96 patients (61 male, mean age 10.7 years) at a mean follow-up interval of 58.8+/-32.1 months (minimum 2 years) following PVBD. The patients were divided into three groups based on the residual gradients at valvular and infundibular levels immediately following PVBD as assessed by pull-back of an end-hole catheter across the right ventricular outflow tract: Group A with minor pressure gradients at both valvular and infundibular levels of less than 30 mmHg (n=60, 62.5%), Group B with predominantly infundibular gradients of more than 30 mmHg with a valvular gradient of less than 30 mmHg (n=27, 28.1%), and Group C with a residual valvular gradient of greater than 30 mmHg irrespective of the infundibular gradient (n=9, 9.4%). Demographic characteristics, hemodynamic parameters and procedural variables were correlated with the change in gradient at follow-up (late fall) and with long-term results. RESULTS: The mean follow-up trans-pulmonary gradient was 20+/-14 mmHg which was significantly lower than that immediately post-PVBD (43+/-32 mmHg), P<0.001. The late fall (mean 24+/-29, range -55 to 110 mmHg) varied widely depending upon the acute result group: patients in Groups A and B showed significant late fall of 9+/-12 mmHg (P<0.05 for follow-up gradient compared to that following PVBD) and 58+/-31 mmHg (P<0.0001), respectively, while patients in Group C showed an insignificant late fall of 14+/-37 mmHg (P=0.21). In particular, each one of the patients in Group B showed decrease in trans-pulmonary gradients. On multivariate analysis, the extent of infundibular gradient emerged as the most important predictor of late fall (coefficient of determination 75%, P<0.0001). Patients who underwent PVBD at less than 2 years of age had a significantly greater late fall (41+/-33 mmHg) as compared to older patients (22+/-25 mmHg), P<0.05. A sub-optimal long-term result (transpulmonary gradient >25 mmHg, n=24) was significantly related to older age (P<0.001), dysplastic valve morphology (P=0.002), greater baseline trans-pulmonary gradients (P<0.001) and higher post-PVBD gradients (P=0.04). CONCLUSIONS: The long-term course of patients following PVBD depends upon the site and magnitude of the residual gradients. Even high residual infundibular gradients show marked reduction at follow-up, especially in infancy.

Adolescent↗

Analysis of the CD40/CD40L role in the sustenance of alloreactive antibody production.

CD40 ligand (CD40L) is important for T/B lymphocyte interaction. To understand the cellular basis of humoral allosensitization we, therefore: (1) measured CD40L protein and gene expression in sensitized and non-sensitized uremic unactivated peripheral CD4+ T lymphocytes; (2) studied the impact of blocking the CD40/CD40L pathway on alloreactive antibody (allo-Ab) production by engrafted sensitized PBLs into severe combined immunodeficient (SCID) mice after in vitro preactivation with IL2/LPs/HLA class II allopeptides and adjuvants as a potent stimulus to produce allo-Ab (Shoker et al. Transplantation 1999;68;1188); and (3) studied the modifying effect of CD40/CD40L blockade on T helper type I and II cytokine gene expression in the respective mice spleen. The CD40L protein was measured by flow cytometry and the gene expression was measured by quantitative RT-PCR. Alloreactive antibodies (alo-Abs) produced by sensitized PBLs engrafted into SCID mice with and without blockade of the CD40 receptor were measured by the PRA-STAT ELISA method. The modifying effects of CD40 blocking on allo-Ab production and cytokine gene expression by the engrafted cells measured by RT-PCR were then compared. There was no detectable CD40L protein expression in either the uremic or the control groups. The CD40L gene expression of 0.04 +/- 0.02 attomoles (aM) in the sensitized group was significantly higher than in the non-sensitized patients (0.009 +/- 0.007 aM, P < 0.0001) or the control CD4+ T cells (0.016 +/- 0.004 aM, P < 0.001). Blockade of the CD40 receptor abrogated the production of allo-Ab antibodies by the engrafted sensitized cells in 60% of the tested mice (n = 10); decreased the mean +/- S.D. optic density of allo-Ab to 0.1 +/- 0.13 and the mean +/- S.D. PRA to 12 + 16). In the presence of the control Ab, allo-Ab production in SCID sera was present in 100% of the 10 SCID mice tested; the mean +/- S.D. PRA was 75 +/- 20, and the mean + S.D. OD activity was 0.412 +/- 0.17. All cytokine genes were, otherwise, expressed in the presence or absence of CD40 blockade. The results suggest a potential role of an enhanced CD40/CD40L interaction in the sustenance of alloreactive antibody production without significant deviation to T helper-like I or II responses. Blocking the CD40/CD40L pathway may have a potential therapeutic benefit to treat sensitized uremic patients.

Adjuvants, Immunologic↗

Univentricular repair in children under 2 years of age: early and midterm results.

BACKGROUND: Encouraging results have been obtained from early univentricular repair. Our study was designed to assess the impact of young age (less than 2 years) on the outcome of univentricular repair. PATIENTS AND METHODS: Between January 1992 and December 1998, 65 out of 311 patients undergoing univentricular repair at the All India Institute of Medical Sciences, New Delhi, were less than 2 years of age. We compared these 65 carefully selected patients (group 1) with the 246 patients who were more than 2 years of age (group 2). Since 1994, all patients of both groups had a fenestration of the intra-atrial baffle. RESULTS: The early mortality rate was 9.2% in group 1 and 7.7% in group 2. The overall Fontan failure rate was 12.3% in group 1 and 12.2% in group 2. In group 1, a higher incidence of Fontan failure was noted in patients with suboptimal weight, non-tricuspid atresia morphology, nonfenestrated Fontan and those who did not comply with more than two of Choussat's criteria, but the values were not statistically significant. Aortic cross-clamp time of more than 60 min was the only and highly significant predictor of Fontan failure (P < 0.01). The overall effusion rate was 24.05% in group 1 and 27.98% in group 2. In group 1, patients weighing less than 10 kg (P = 0.0007), without fenestration of the atrial baffle (P < 0.05) and with systemic ventricular dysfunction (P < 0.001), systemic ventricular end-diastolic pressure of more than 12 mmHg (P < 0.001), mean pulmonary artery pressure of more than 15 mmHg (P < 0.001) and aortic crossclamp time of more than 60 min (P < 0.01), were all found to be significant risk factors of pleural effusion. Pulmonary artery distortion needing reconstruction did not increase the Fontan failure or effusion rates. Oxygen saturation ranged from 85 to 94% (mean 89%) in patients having a functioning fenestration at a mean follow-up period of 30 months. The actuarial survival at 84 months was 90 +/- 0.04% in group 1 and 88 +/- 0.02% in group 2. CONCLUSIONS: Our results suggest that carefully selected patients under 2 years of age are suitable candidates for one-stage univentricular repair and that survival is not significantly different from that of older patients. Routine fenestration of the intra-atrial baffle is an option available to ameliorate morbidity and obviate mortality. Non-compliance with more than two of Choussat's criteria appears to be additive in unsatisfactory outcome.

Journal Article↗